This invention relates to compositions and methods useful to protect human or animal eye cell layers and tissue subject to exposure to trauma. More particularly, the invention relates to compositions and methods involving hyaluronate fractions having differing molecular weights for protecting eye cell layers and tissues exposed to trauma, for example, during surgery.
When the natural lens of the eye becomes hazy or clouded, surgery is often indicated to remove the impaired lens. The current trend in such surgery is toward breaking the lens into a plurality of particles and then removing the particles, e.g., using the conventional phacoemulsification procedure. The use of a protective agent, in particular a viscoelastic fluid, that adheres to and protects the corneal endothelium during the surgical procedure is highly beneficial. Fluids containing high molecular weight range hyaluronates, that is hyaluronates having weight average molecular weights over 750,000, do not provide entirely acceptable adhesion to and/or protection of the corneal endothelium during certain surgical procedures. An example of such a fluid is that sold by Pharmacia Ophthalmics of Monrovia, Calif. under the trademark Healon.RTM..
Formulations which include hyaluronic acid having a molecular weight of at least about 750,000, and preferably at least about 1,200,000 are disclosed in Balazs U.S. Pat. No. 4,141,973. Such formulations, which are not described in this patent as including any lower molecular weight hyaluronic acid, are disclosed as being useful in a number of applications, such as in the replacement of the aqueous humor after various intraocular surgical procedures, and as a biological prosthesis in the anterior chamber after cataract surgery.
Another formulation which includes high molecular weight hyaluronate (molecular weight of 1.times.10.sup.6 to 4.5.times.10.sup.6) is that disclosed in Balazs U.S. Pat. No. 4,303,672. The cosmetic formulations of this patent also include a low molecular weight hyaluronate fraction (molecular weight of 10,000 to 200,000) and protein in an amount ranging from 50% to 400% the weight of the hyaluronate. Such compositions are taught as having emollient, moisturizing, elasticizing and lubricating properties where applied to the skin. Such protein-containing hyaluronate compositions are not ophthalmically acceptable and would not be useful as protective agents in eye surgery.
Nimrod et al U.S. Pat. No. 4,784,990 discloses methods for producing cosmetic grade sodium hyaluronate containing between about 87% and 91% sodium hyaluronate of an average molecular weight between about 700,000 and 1,500,000 daltons, and clinical grade sodium hyaluronate with an average molecular weight of more than 700,000 daltons, usually in the range of from about 2 million to about 3 million daltons. The cosmetic grade of this material is not intended for use in the eye.
A sodium hyaluronate formulation, sold by Allergan, Inc. under the trademark Vitrax.RTM., includes sodium hyaluronate having an average molecular weight of about 500,000 in a balanced salt aqueous solution. This formulation, which is useful in ophthalmic applications, does not contain a substantial amount of sodium hyaluronate having an average molecular weight in excess of about 1 million.
Bracke et al U.S. Pat. No. 4,517,295 discloses hyaluronic acid having an average molecular weight of about 55,000 which is produced from bacterial sources. Such hyaluronic acid is disclosed as having potentially significant use as an eye drop ingredient and as an ingredient of cosmetic formulations, as well as being useful in post-surgical applications for reducing complications due to fibrotic response and/or adhesion formation. This patent does not disclose the use of such hyaluronic acid as a protective agent in eye surgery.
Other formulations incorporate combinations of different materials, such as sodium hyaluronate and chondroitin sulfate. This type of product is described in Australian Patent 555,747. A product for use in providing protection during eye surgery and including sodium hyaluronate and chondroitin sulfate is that sold by Alcon Surgical, Inc. of Forth Worth, Tex. under the trademark Viscoat. Sources of chondroitin sulfate often include significant amounts of protein which need to be removed, using relatively complex and expensive separation techniques, before the purified chondroitin sulfate can be used in the eye.
There continues to be a need for compositions useful in protecting ocular or eye cell layers and tissues exposed to trauma, in particular trauma involved in ophthalmic surgical procedures.